Age-related macular degeneration (ARMD) is the leading cause of vision loss in the western world. Non-neovascular (dry) ARMD is characterized by poorly functioning retinal pigment epithelial (RPE) cells. Strategies to replace damaged RPE cells may prevent vision deterioration. Adult ciliary body epithelial cells are a patient specific, multipotent cell source that can differentiate into cells that mimic RPE cells. We intend to investigate the regulatory pathways that guide adult ciliary body progenitor cell specification into an RPE lineage. SOX2 and PAX6 are transcription factors that are attractive candidates for regulating this pathway because they are essential for normal eye development and are expressed in retinal stem cells. We intend to use transgenic mouse models to ablate or express SOX2 and PAX6 to dissect the role of these transcription factors in progenitor cell biology. My long-term scientific goal is to develop a strategy to replace damaged RPE cells for patients with non-neovascular ARMD. This project will be completed in collaboration with Dr. Larysa Pevny, an expert stem cell scientist and developmental biologist, who has significant experience in studying SOX2 and PAX6 in retinal development. In her research, she has developed the genetic tools to answer the hypotheses in this proposal and has agreed to serve as my primary mentor for this project. Drs. Patterson, Meredith, and McGahan will provide career mentorship and monitor scientific progress for the duration of this grant proposal. Their purpose will be to ensure that I am meeting incremental goals on the way to becoming an independently NIH funded physician scientist.